Respiratory syncytial virus (RSV) is the most important case of respiratory infection in childhood. Efforts to control RSV infections through immunoprophylaxis have failed in that neither inactivated nor live attenuated vaccines protect against challenge. Natural disease also immunizes poorly in small infants: reinfections tend to occur frequently, with production of clinical illness. It is this combination of puzzles which this research proposal intends to investigate through examining the antigenic heterogeneity of RSV strains and the specificity and function of the immune response with emphasis on disease in infants. In particular, we intend to 1) Analyze in detail the antigen content of human secretions during RSV infection. 2) Characterize the antigenic heterogeneity of RSV by means of monoclonal antibodies, performing prevalence surveys in eastern Massachusetts of RSV strains separable by these techniques. 3) Examine the importance of antigenic heterogeneity in relation to immunity to infection. 4) Describe in greater detail the secretory antibody response of infants, children and adults infected or reinfected with RSV. Antibody to individual proteins and glycoproteins of selected RSV strains will be studied with monoclonal antibody solid phase immunoassays. 5) Make correlations between antibody in secretions or sera, functions such as neutralization or antibody-dependent cellular cytotoxicity, and susceptibility to or protection against reinfection.